Comparative study between manitol and sodium picosulfate with magnesium oxide solutions in the preparation for colonoscopy

ABSTRACT This prospective, randomized and double-blind study aims to compare two different protocols used for bowel preparation in patients scheduled for colonoscopy. The protocols were composed by solutions of Mannitol or sodium picosulfate combined with magnesium oxide. Patients from the proctology outpatient clinic of the General Surgery Unit of the Regional Hospital of Asa Norte (HRAN) comprised the sample of this study. Both the patients and the colonoscopist had no prior knowledge of the substance used to prepare bowel, which was randomly distributed among the participants. Both protocols demonstrated good and similar results regarding the efficiency of colon preparation, although the review of literature shows a difference in favor of preparation made with Mannitol solution regarding the colon neatness during the exam. In line with the literature, patients who used Mannitol solution had more side effects, highlighting the significant difference found for vomiting and sleep impairment. The preparation with Sodium Picosulfate with Magnesium Oxide was significantly superior in relation to the ease of ingestion perceived by the patients.

The colon cleansing agent with an adequate profile should have reduced periods of ingestion and evacuation, while emptying all fecal material, solid or liquid, from the colon and rectum.It is also important to avoid gross or histological changes in the colonic mucosa, hydroelectrolytic variations, and discomfort by the patient 5,7 .
The tolerability of the preparation by the patient is of utmost importance, since the inability to complete the steps of the preparation leads to worse cleaning conditions for the examination, affecting patient compliance to screening programs 7,8 .In addition to patient tolerability, there is a concern in the literature about ease of administration, affordability, and how to prevent the preparation from resulting in the formation of explosive gases 3 .
Over the years, most professionals have preferred anterograde colon preparation due to the quality of cleaning obtained and the patient's comfort.
The regimens currently available can be divided into two groups, consisting of large-volume, osmotically balanced substances, or low-volume, osmotically active ones.
Larger volume preparations tend to be less tolerated 8 .
Balancing the quality and acceptability of the preparation remains a challenge.In this context, two types of preparation were chosen for analysis and comparison in this work, those using Mannitol (Group M) and those using Sodium Picosulfate with Magnesium Oxide (Group P).The choice is due to the wide availability and use for the preparation of colonoscopy in clinical practice 8 .
A member of the group of osmotic laxatives, mannitol is a derivative of mannose and is administered orally in a hypertonic solution that is not absorbed from the gastrointestinal tract.It tastes sweet and is administered diluted in juice for better tolerability.The patient needs to ingest a large volume, which can be divided over a long period of time (5-6h).However, a considerable number of patients have difficulty in ingesting the preparation, which can affect its result.Some studies have pointed to the risk of the fermentation of orally ingested mannose, causing the production of potentially explosive gases in the intestine, although the safety has been demonstrated in several studies.
The combined preparation of sodium picosulfate with magnesium oxide is widely used, with good results documented in 85% of patients.Sodium picosulfate is a cathartic stimulant that is activated by colonic bacteria and acts primarily in the left colon.Magnesium oxide is an osmotic purgative that cleans the proximal colon 3 .Some authors also recommend a restrictive diet the day before to aid in the preparation, in addition to the combined use of bisacodyl to enhance the action of the other preparations.Bisacodyl is a contact laxative derived from diphenylmethane, with a hydragogue and anti-resorptive effect.It stimulates colonic peristalsis after hydrolysis in the mucosa of the large intestine, promoting accumulation of water and, consequently, of electrolytes in the colonic lumen 3 .
Failure to prepare the colon for colonoscopy can result in failure to detect pathological lesions, in addition to cancellation and interruption of the procedure.The negative consequences of inadequate preparation are high for the health system, with significant harm to patient satisfaction.Failure of the procedure may result in delayed diagnosis and prolonged hospitalization 3 .
Recent studies have shown that demographic variables and clinical characteristics can influence the quality outcome of colonoscopy.These findings highlight the importance for the continuity of the study on the preparation of colonoscopy, especially in the context of the public health service, which its inherent peculiarities, both structural and of patients.In the medical literature on the subject, the Brazilian population is rarely studied 9 .
Being one of the most prevalent neoplasms in the world, colorectal cancer is the fourth leading cause of cancer-related death in both sexes combined.Among the risk factors for colorectal cancer are age (advanced) and the region of the globe, the most developed nations being those with the highest mortality rate.An increase of 80% in colorectal cancer is expected by the year 2030 due to demographic changes.South America underwent rapid epidemiological change caused by factors such as demographic transition, socioeconomic changes, and increased rates of overweight and obesity -with a dietary pattern based on sugars and saturated fats associated with a sedentary lifestyle.As a result, there was a decrease in the incidence of cancers related to infections in relation to cancers typically diagnosed in countries with better human development.Mortality in these cases is inversely related to early detection.Brazil presents an increase in the demand for preventive exams, such as colonoscopy.
The impact of morbidity and mortality can be related to differences in infrastructure and access to health care and specialized exams 9 .
Due to the status of colorectal cancer and the limited screening capacity in countries with transitioning populations, the implementation of comprehensive colorectal cancer monitoring is imperative.Quality data must be generated to improve knowledge on the subject 9 .As a primary objective, we evaluated the quality of the preparation regarding cleanliness of the organ during the examination and adequate visualization according to the Boston scale.As a secondary objective, the aim was to evaluate the acceptability, the ease of use of the preparation, in addition to the occurrence of electrolyte imbalances and side effects.

METHODS
This is a randomized, double-blinded study.
The selected sample consists of patients scheduled to undergo colonoscopy in a proctology outpatient clinic of a public hospital, from August 2017 to March 2018.
We excluded patients who did not show up on the scheduled date, those who refused to participate, and those who were unable to follow the preparation instructions.
Patients scheduled for colonoscopy received guidance on preparation in the week prior to the exam.

The selection of the solution -Mannitol or Sodium
Picosulfate with Magnesium Oxide -to be used in each patient was performed by simple randomization.The patients were not aware of the substance used, as the preparation was delivered without identification.The colonoscopy exam was routinely performed at 1:00 pm on Mondays, according to the service's routine.
All patients were previously instructed about the preparation and received a printed copy of the instructions when they received the preparation material, that is, in the week before the exam.On that occasion, doubts regarding the exam were clarified and the patients were invited to sign a consent form to participate in the study.
In both preparation methods, two bisacodyl tablets were used in the morning of the day before the exam, associated with a minimal residue diet.On the day of the exam, an exclusive liquid diet was recommended until 11 am, after which absolute fasting was instituted.
The mannitol preparation group (Group M) received a solution of 750mL of 20% Mannitol, to be diluted in 750mL of strained orange or lemon juice.
Ingestion was divided into aliquots of approximately 200mL every 15 minutes and started at 6:00 am on the day of the exam.
For the preparation group with Sodium Picosulphate and Magnesium Oxide (Group P), the drug was presented in a sachet, to be diluted in 150mL of water for ingestion.In this group, the ingestion of two sachets of the solution was recommended.The first on the day before the exam, followed by the ingestion of at least five 250ml cups of clear liquid without residues.
And the second, on the day of the exam, at 6:00 am, followed by the ingestion of at least three 250ml cups of clear liquids without residues.Shortly before the exam, all patients answered a standard questionnaire, with information about demographic data, vital signs, exam indication, bowel habits, preparation tolerance, side effects, flavor, and other possible aspects related to the preparation.
The colonoscopist was not aware of the preparation used by the patient and assessed the exam with a quality of preparation score according to the Boston scale, in addition to the description of the colonoscopic findings.
For statistical analysis, we present numerical variables as mean and standard deviation, and categorical variables, as absolute and relative frequency.Comparison between groups was performed using the Mann-Whitney U, Chi-square, or Fisher's exact tests.The significance level adopted was p≥0.05.All analyzes were performed using the Statistical Package for Social Sciences (SPSS) software, version 22.0.Regarding the categorical variables, we observed no statistically significant differences between groups.The main indications for colonoscopy were digestive bleeding (35.6%), abdominal pain (16.7%), family history of cancer (15.6%), investigation of neoplastic focus (12.2%), and weight loss (11.1%).
When analyzing the effectiveness of the protocol used for colon preparation, the result of the Boston Scale applied to both groups was considered satisfactory for most patients (Group M: 86.4%; Group P: 88.9%; p=0.734).
Additionally, serum sodium and potassium levels were collected immediately before colonoscopy, with no significant differences observed between groups (p>0.05)regarding variations in normality and electrolyte disturbances.
In 17% of the colonoscopic examinations biopsies were performed as indicated by the colonoscopist.
Tubular adenoma with low-grade dysplasia was found in 43.7%, adenocarcinoma in 18.7%, chronic colitis in 18.7%, and nonspecific chronic inflammatory process in 12.5%.Tubular adenoma with high-grade dysplasia, ileitis, chronic proctitis, chronic inflammatory bowel disease with microabscesses, or low-grade tubulovillous adenoma were observed in 6.2% of cases.

DISCUSSION
The Given the importance of proper colon preparation for performing the colonoscopy exam, several studies have focused on the efficacy, safety, and tolerability of different forms of preparation.Under these circumstances, the present study aims to compare protocols based on two different solutions, the Sodium Picosulphate solution and the Mannitol one, as methods of colon preparation for the colonoscopy exam, to assess which solution provides better results.
adequate evaluation and comparison of preparation methods for colonoscopy considered three factors.The first was the effectiveness of colon cleansing assessed using the Boston scale.The second was safety and side effects.The third was tolerability, which can influence adherence to the use of preparations by patients.

Figure 2 .
Figure 2. Comparison of side effects of patients taking the preparation in Group M (n=47) and in Group P (n=36).*Statistically significant difference.

Figure 3 .
Figure 3.Comparison of the Boston Scale Result of patients in Group M and Group P.
patients who underwent colonoscopy from March 2017 to July 2018 participated in this study.Of these, 55.6% belonged to Group M and 44.4%, to Group P. The continuous variables for the characterization of the sample are presented in the Table 1.It is noteworthy that
BMI: Body de Mass Index; HR: Heart Rate; BP: Blood Pressure.
VissociComparative study between manitol and sodium picosulfate with magnesium oxide solutions in the preparation for colonoscopy Regarding the efficiency of the preparations, this study showed that both had good results and that they were very similar, with no statistically significant difference.This data is corroborated by the results of Miki et al. in a work carried out in the state of São Paulo in 2008 10 .However, both Müller et al., in the state of higher frequency of vomiting among individuals in Group